Wednesday, November 23, 2005

Mechanism of Absorption of Ultrafine Particles

A second big bang for occupational and environmental health is the late 1990's observation of systemic health effects from insoluble inhaled particles. The Dodger reminds the reader these health effects include mortality from cardiac causes from exposures within the EPA community particle standard.

These observations sparked laboratory toxicology, much the way the discovery of mortality associated with cigarette smoking sparked laboratory work. Unlike the cigarette toxicology, which only recently has replicated lung cancer mortality by inhalation, the particle project very quickly yielded results which provided biological plausibility to the epidemiological findings.

Here, the investigators demonstrate the absorption of the archetypical non toxic non soluble titanium dioxide particles through the lumen and into cells.

Environ Health Perspect.
2005 Nov;113(11):1555-60.

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Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells.

Geiser M, Rothen-Rutishauser B, Kapp N, Schurch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J, Gehr P.

Institute for Anatomy, University of Bern, Bern, Switzerland.

High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < size="3">Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 microm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential.

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